Epidemiology suggests that acute injury due to SM exposure leads to severe and recurring, chronic disease. Our Center's overall goal is to develop animal models of SM exposure to identify and test therapeutic interventions specifically for use in a triage setting as specifically outlined within the RFA. In order to accomplish our overall goal, Project 1 is charged with identifying biomarkers of exposure that represent the variety of human conditions and to develop a diagnostic test for use in a civilian triage setting of SM-exposure as specifically outlined within the RFA. To test our overarching hypothesis we have developed a comprehensive center around sulfur mustard exposure that (1) will bring forth scientific basis for therapeutics and diagnostics and (2) will enable GLP testing of such therapeutics and diagnostics. Project 1 brings together scientists from Lovelace Biomedical and Environmental Research Institute and University of Florida in a highly synergistic manner to bring forth a diagnostic countermeasure in the most efficient manner to what the CIA, DOD and the Congressional Research Service (CRS) have ranked as the highest probability agent to be used in a chemical attack, sulfur mustard. Specifically, Project 1 will identify and validate biomarkers (known and to be identified) in association with disease outcome and therapeutic intervention (Dr. Boggs, Lovelace Biomedical and Environmental Research Institute). These biomarkers will feed directly into the development of a diagnostic strip test (Drs. Tan and Batich, University of Florida). Our long-range goal is to develop diagnostic medical countermeasures against chemical threat agents. The overarching goal of this research Program is to enhance our diagnostic and treatment response capabilities. The specific outcome of this proposal, which is the next step towards the long-term goal, is to determine a set of biomarkers that can be used to diagnose SM-induce injury and disease. The rationale is that by identifying biologically meaningful biomarkers, a diagnostic test can be developed to aid in countermeasures against SM exposure. The objective of this study is to determine a comprehensive set of biomarkers associated with SM-exposure and correlate with therapeutic agents to be used as a diagnostic tool. Our general hypothesis is alterations in protein expression as a result of SM exposure can be used as biomarkers to predict effective therapeutics. The following specific aims will test our general hypothesis: (1) To evaluate changes in known proteins in a dose, time and disease outcome from exposure to SM; (2) To determine a new set of biomarkers related to SM exposure and disease outcome; (3) To evaluate biomarkers of exposure on the efficacy of therapeutic agents; and (4) Design, construct and test a diagnostic strip to assess the molecular profile of SM injury.